Self-Study Modules on Tuberculosis

Treatment of Latent Tuberculosis Infection and Tuberculosis

Disease 

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Introduce Module 4

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Module 4: Objectives

At completion of this module, learners will be able to:

List groups of people who should receive high priority for latent TB infection (LTBI) treatment

Describe treatment regimens for LTBI

Describe treatment regimens for TB disease

Describe principles of preventing drug resistance

Describe patient monitoring during LTBI and TB disease treatment

Describe TB treatment adherence strategies

List common adverse reactions to drugs used to treat LTBI and TB disease

State objectives of presentation 

Background and Objectives - Module 4, p. 1

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Treatment of LTBI

Patient Medical Evaluation

LTBI Treatment Regimens

Special Considerations for LTBI Treatment

Treatment of TB Disease

TB Disease Treatment Regimens

Module 4: Overview

Review slide content 

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Treatment of TB Disease (cont.)

Special Considerations and Alternative Treatment Regimens

Treatment and Monitoring Plan and Adverse Reactions

Adherence and Evaluating Patients’ Response to Treatment

Role of Public Health Workers

Case Studies

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Module 4:  Overview (cont.)

Review slide content

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Treatment of Latent TB Infection (LTBI)

Introduce section

Ask who should be treated for LTBI

Ask why people with LTBI should be treated 

Treatment of LTBI - Module 4, pp. 4-21

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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LTBI is treated to prevent the development of TB disease

LTBI is treated with medication 

Treatment of LTBI (1)

Review slide content

Treatment of LTBI - Module 4, p. 4

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Targeted testing should be used to identify and treat people who are:

At high risk for exposure to or infection with M. tuberculosis

At high risk for developing TB disease once infected with M. tuberculosis

People in these groups should receive high priority for LTBI treatment if they have a positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA)

Treatment of LTBI (2)

Explain that some groups are at higher risk for TB than others 

Review slide content

Treatment of LTBI - Module 4, p. 4

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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High Priority for LTBI Treatment (1)

High-priority groups for LTBI treatment if positive IGRA or TST result of > 5 mm

Recent contacts of people with infectious TB disease

People living with HIV

People with chest x-ray findings suggestive of previous TB disease

Patients with an organ transplant

Other immunosuppressed patients

Review slide content

Explain that other immunosuppressed patients include patients on prolonged therapy with corticosteroids equivalent to/greater than 15mg per day of prednisone for one month or more or those taking TNF-alpha antagonists

High Priority for LTBI Treatment - Module 4, p. 5

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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High Priority for LTBI Treatment (2)

High-priority groups for LTBI treatment if positive IGRA or TST result of  > 10 mm:

People who have come to U.S. from countries where TB is common

People who abuse drugs

People who live or work in high-risk congregate settings

People who work in mycobacteriology laboratories

Review slide content

High Priority for LTBI Treatment - Module 4, p. 5

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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High-priority groups for LTBI treatment if positive IGRA or TST result of  > 10 mm (cont.):

People with medical conditions that increase risk of TB disease

Children younger than 5 years of age

Infants, children, and adolescents exposed to adults in high-risk groups

High Priority for LTBI Treatment (3)

Review slide content

High Priority for LTBI Treatment - Module 4, p. 5

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Individuals without any risk factors generally should not be tested for TB infection 

However, individuals with no risk factors who are tested and have a positive IGRA or TST result of > 15 mm should be evaluated for LTBI treatment

Low Priority for LTBI Treatment

Review slide content

Low Priority for LTBI Treatment - Module 4, p. 4

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Treatment of Latent TB Infection (LTBI)Patient Medical Evaluation

Introduce section

Patient Medical Evaluation – Module 4, pp. 5-6

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Medical Evaluation (1)

   Medical evaluations should be done to:

Exclude possibility of TB disease

Determine whether patient has ever been treated for TB infection or TB disease

Find out if patient has any medical conditions that may complicate therapy

Establish and build rapport with patient

Review slide content 

Patient Medical Evaluation – Module 4, pp. 5-6

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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1.  Exclude possibility of TB disease

Treating TB disease with LTBI treatment regimen can lead to drug resistance

Clinicians should determine if the patient has symptoms of TB disease

Clinicians should evaluate the patient with a chest x-ray

Patients with symptoms or chest x-ray findings of TB disease should be given TB disease treatment, not LTBI treatment

Patient Medical Evaluation (2)

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Review slide content 

Explain that treating TB disease with an LTBI treatment regimen can lead to drug resistance since LTBI is usually only treated with a single drug

Patient Medal Evaluation – Module 4, p. 5

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Medical Evaluation (3)

Determine whether patient has ever been

	treated for TB infection or TB disease

Patients who have been adequately treated should not be treated again

TST or IGRA results cannot determine if patient has received treatment for LTBI or TB disease; or if they have been re-infected after treatment

15

Review slide content 

Explain that people who have a positive TST reaction will have another positive reaction if they are skin tested later in their lives, regardless of whether they have received treatment

Note that there is not enough data on the ability of either test to detect re-infection after treatment for both LTBI and TB disease

Patient Medical Evaluation – Module 4, pp. 5-6

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Medical Evaluation (4)

3.   Find out if patient has any medical conditions that may complicate therapy or require more careful monitoring. These patients include: 

People living with HIV

People with history of liver disorder or disease

People who use alcohol regularly

Women who are pregnant or just had a baby (within 3 months of delivery)

People who are taking other medications that may increase the risk of hepatitis

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Review slide content 

Patient Medical Evaluation – Module 4, p. 6

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Medical Evaluation (5)

For patients with the medical conditions listed on the previous slide, baseline laboratory liver function tests (to detect injury to liver) are recommended before starting LTBI treatment.

Review slide content 

Patient Medical Evaluation – Module 4, p. 6

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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It is important to find out if:

Patient has ever had adverse reactions to LTBI drugs

Patient is currently on medications that may interact with LTBI drugs

Patient Medical Evaluation (6)

Review slide content 

Patient Medical Evaluation – Module 4, p. 6

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Medical Evaluation (7)

4.   Establish and build rapport with patient

Health care workers (HCWs) should highlight important aspects of treatment, such as:

Benefits of treatment

Importance of adherence to treatment

Possible adverse reactions

Establishment of a follow-up plan

Review slide content 

Patient Medical Evaluation – Module 4, p. 6

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Medical Evaluation (8)

Because of the interaction between TB and HIV, HCWs should also recommend that patients undergo HIV counseling and testing

Review slide content 

Patient Medical Evaluation – Module 4, p. 6

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Treatment of Latent TB Infection (LTBI)LTBI Treatment Regimens

Introduce section

LTBI Treatment Regimens – Module 4, pp. 6-9

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Isoniazid (INH) daily for 9 months is very effective in preventing the development of TB disease

INH may also be given for 6 months

Cost effective and patients may find it easier to adhere, BUT:

Not as effective if given for less than 6 months

Not recommended for people living with HIV, individuals with previous TB disease, or children

LTBI Treatment Regimens (1)Isoniazid

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Explain that there are several treatment regimens available for LTBI

Note that until recently, the standard regimen for LTBI was INH for 9 months

Review slide content

Regimens for LTBI Treatment – Module 4, p. 7

LTBI Treatment Regimens (2)Isoniazid and Rifapentine (12-Dose Regimen)

Combination of INH and rifapentine (RPT) given in 12, once-a-week doses under DOT, if possible

Recommended for patients who:

Are 12 years of age or older

Were recently exposed to infectious TB

Have a TST or IGRA conversion from negative to positive

Have chest x-ray findings of previous TB disease

Regimen may be used in otherwise healthy HIV-infected persons who are:

12 years of age or older

Not on antiretroviral therapy (ART), except those taking an efavirenz or raltegravir-based ART regimen

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Review slide content

Regimens for LTBI Treatment – Module 4, p. 7

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LTBI Treatment Regimens (3)Isoniazid and Rifapentine (12-Dose Regimen)

This regimen is not recommended for

Children younger than 2 years of age

People with HIV/AIDS who are taking certain ART regimens

People presumed to be infected with isoniazid or rifampin-resistant M. tuberculosis

Pregnant women or women expecting to become pregnant within the 12–week regimen

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Review slide content

Regimens for LTBI Treatment – Module 4, p. 7

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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LTBI Treatment Regimens (4)Rifampin

Rifampin (RIF) is also recommended for people with a positive TST or IGRA result

Especially if the person has been exposed to INH-resistant TB

RIF should be given daily for 4 months

RIF should not be used with certain combinations of ART

In some cases, rifabutin (RFB) may be substituted when RIF cannot be used

25

Review slide content

 Regimens for LTBI Treatment – Module 4, p. 8

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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LTBI Treatment Regimens (5)Rifampin and Pyrazinamide

CDC advises against using a combination of RIF and pyrazinamide (PZA) due to serious side effects such as:

Severe liver injury 

Death

Review slide content

Regimens for LTBI Treatment – Module 4, p. 8

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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LTBI Treatment Regimens (6)
| Drug | Duration(months) | Frequency    | Minimum Dose | Comments                                                                                                                                                     |
|------|------------------|--------------|--------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|
| INH  | 9                | Daily        | 270          | Preferred regimen is daily treatment for 9 monthsDOT must be used with twice-weekly dosing                                                                   |
|      |                  | Twice weekly | 76           |                                                                                                                                                              |
| INH  | 6                | Daily        | 180          | NOT recommended for people living with HIV, children, or people with chest x-rays suggestive of previous TB diseaseDOT must be used with twice-weekly dosing |
|      |                  | Twice weekly | 52           |                                                                                                                                                              |

Table 4.2

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Ask participants to turn to p. 8 (if participants have print-based modules)

Explain that this table describes the various LTBI treatment regimens

Review slide content 

Regimens for LTBI Treatment – Module 4, pp. 8-9

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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LTBI Treatment Regimens (7)
| Drug        | Duration(months)                                                                                                                     | Frequency   | Minimum Dose | Comments                                                                                                                                                                                                                                         |
|-------------|--------------------------------------------------------------------------------------------------------------------------------------|-------------|--------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| INH and RPT | 3                                                                                                                                    | Once Weekly | 12           | NOT recommended for children younger than 2 years of age, HIV-infected patients taking certain ART regimens, patients with resumed INH or RIF-resistant TB, pregnant women, or women expecting to become pregnantDOT is recommended, if possible |
| RIF         | 4                                                                                                                                    | Daily       | 120          | Recommended for patients who have INH-resistant TB NOT recommended for HIV-infected patients on certain combinations of ART. RFB may be used instead for some patients.                                                                          |
| RIF/PZA     | Due to the reports of severe liver injury and deaths, RIF and PZA combinations generally should not be offered for treatment of LTBI |             |              |                                                                                                                                                                                                                                                  |

Table 4.2 

Review slide content 

Regimens for LTBI Treatment – Module 4, pp. 8-9

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Treatment of LTBI Study Question 4.1

	What is the purpose of LTBI treatment? 

		To prevent people with latent TB infection  	from developing TB disease.

Introduce study questions

Ask participants to turn to p. 10 (if participants have print-based modules)

Read question 

Ask participants for answers

Answers – Module 4, p. 49

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	Which groups of people should receive high-priority for LTBI treatment if they have a positive IGRA or TST result of > 5 mm?  Name 5.  

Recent contacts of people with infectious TB disease

People living with HIV

People with chest x-ray findings suggestive of previous TB disease

Patients with an organ transplant

Other immunosuppressed patients 				

Treatment of LTBI Study Question 4.2

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Read question 

Ask participants for answers

Answers – Module 4, p. 49

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	Which groups of people should receive high priority for LTBI treatment if they have a positive IGRA result or a TST reaction that is > 10 mm? Name 7. 

People who come to the U.S. from areas of the world where TB is common

People who abuse drugs

People who live or work in high-risk congregate settings

People who work in mycobacteriology laboratories

People with medical conditions that increase risk of TB disease

Children younger than 5 years of age

Infants, children, and adolescents exposed to adults in high-risk groups

Treatment of LTBI Study Question 4.3

Ask for a volunteer to read question 

Ask participants for answers

Answers – Module 4, p. 49

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	List 4 regimens that are approved for the treatment of LTBI.

Isoniazid for 9 months

Isoniazid for 6 months

Isoniazid and rifapentine for 12, once-weekly doses (12-dose regimen)

Rifampin for 4 months

LTBI Treatment Regimens Study Question 4.4

Read question 

Ask participants for answers

Answers – Module 4, p. 49

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Treatment of Latent TB Infection (LTBI)Special Considerations for LTBI Treatment

Introduce section

Special Considerations for LTBI Treatment – Module 4, pp. 11-14

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (1)Directly Observed Therapy (DOT)

DOT is when a HCW or another designated person watches a patient swallow each dose of medication

Used to help patients adhere to treatment

Should be considered for people who are at high risk for TB or suspected to be non-adherent

Recommended for intermittent therapy

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Review slide content

Explain that intermittent therapy is when regimens are given once or twice weekly

Directly Observed Therapy – Module 4, p. 11

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (2)Contacts

Contacts are people who have been exposed to someone with infectious TB disease

Contacts should be quickly identified, located, and assessed for LTBI and TB disease

If TST or IGRA result is positive, contacts should be given high priority for LTBI treatment (once TB disease is ruled out)

If TST or IGRA result is negative, contacts should be retested in 8 to 10 weeks

Review slide content 

Explain that contacts should be retested after 8 to 10 weeks if their result is negative because sometimes it can take 2 to 8 weeks after TB infection for the body’s immune system to produce a response to the TST or IGRA

Contacts – Module 4, p. 11

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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In general, contacts with positive test result and a documented history of completion of LTBI treatment do not need to be retreated

However, retreatment may be necessary for persons at high risk of:

Becoming re-infected

Progressing to TB disease

Special Considerations for LTBI (3)Contacts

Review slide content 

Contacts – Module 4, p. 11

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (4)Contacts at High Risk for Rapid Development of       TB Disease

Some contacts may be started on LTBI treatment even if their test result is negative, and less than 8 to 10 weeks have passed since last exposure to TB; this includes:

Children younger than 5 years of age

People living with HIV

Expert consultation should be sought to determine if contacts with immunocompromised states other than HIV infection could benefit from treatment even if they have a negative TST or IGRA result

Review slide content 

Explain that it is possible that some contacts are infected with M. tuberculosis but have a false-negative TST reaction because less than 8 to 10 weeks have passed since they were last exposed to TB

Contacts at High Risk for TB Disease – Module 4, p. 12

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Once active TB disease is ruled out, contacts at high risk for TB disease should:

Start LTBI treatment

Be retested 8 to 10 weeks after last exposure to TB

If negative test result: stop LTBI treatment

If positive test result: continue LTBI treatment

Contacts living with HIV may be given full course of LTBI treatment even if their second TST or IGRA result is negative

Special Considerations for LTBI (5)Contacts at High Risk for Rapid Development of       TB Disease

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Review slide content 

Explain that LTBI treatment is started to prevent persons from rapidly progressing to TB disease

Contacts at High Risk for TB Disease – Module 4, p. 12

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (6)Infants and Children

Infants and children are more likely to develop life-threatening forms of TB disease

Children younger than 5 years of age who have been exposed to TB should start taking LTBI treatment even if they have a negative TST or IGRA result because they:

Are at high risk for rapidly developing TB disease

May have a false-negative TST reaction

Review slide content 

Infants and Children – Module 4, pp. 12-13

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (7)Infants and Children 

Infants and children should be retested 8 to 10 weeks after last exposure

LTBI treatment can be stopped if ALL of the following conditions are met:

Child is at least 6 months of age

Second TST or IGRA is negative

Second TST or IGRA was done at least 8 weeks after child was last exposed to a person with infectious TB disease

The 12-dose regimen is not recommended for children younger than 2 years of age

40

Review slide content 

Infants and Children – Module 4, p. 13

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (8)Contacts of INH-Resistant TB

Contacts of patients with INH-resistant, but RIF-susceptible TB, may be treated with a 4-month daily regimen of RIF

In some patients, rifabutin (RFB) may be substituted if RIF cannot be used

Review slide content 

Contacts of INH-Resistant TB – Module 4, p. 13

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (9)Contacts of Multidrug-Resistant TB (MDR TB)

The risk for developing TB disease should be considered before recommending LTBI treatment

Contacts of patients with MDR TB

May be treated for 6 to 12 months with an alternative regimen of drugs to which the M. tuberculosis isolate is susceptible

Can be observed for signs and symptoms of TB disease without treatment

All persons with suspected MDR LTBI should be followed and observed for signs and symptoms of TB disease for 2 years, regardless of the treatment regimen

Review slide content

Note that an MDR TB treatment expert should be consulted

Contacts of Multidrug-Resistant TB – Module 4, p. 13

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (10)Pregnant Women

For most pregnant women, LTBI treatment can be delayed until after delivery, unless they have certain risk factors

Immediate treatment should be considered if woman is living with HIV or is a recent TB contact

Preferred LTBI treatment regimen is 9 months of INH with a vitamin B6 supplement 

INH has not been shown to have harmful effects on the fetus

The 12-dose regimen is not recommended for pregnant women or women expecting to become pregnant within the 12-week regimen

43

Review slide content 

Pregnant Women – Module 4, p. 13

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (11)Breastfeeding Women

Women who are breastfeeding can take INH, but should also be given a vitamin B6 supplement

Amount of INH in breast milk is not enough to be considered treatment for infant

44

Review slide content 

Breastfeeding Women – Module 4, p. 14

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBI (12)People Living with HIV

Individuals living with HIV should be treated with 9-month regimen of INH

RIF should not be used for people who are taking certain combinations of ART

Dose-adjusted rifabutin (RFB) may be given

The 12-dose regimen of INH and RPT may be used for people living with HIV who are:

12 years of age or older

Not on ART, except those taking an efavirenz or raltegravir-based ART regimen

Review slide content 

People Living with HIV – Module 4, p. 14

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	What LTBI treatment regimen may be recommended for people with a positive TST or IGRA result who have been exposed to INH-resistant TB? 

	Treatment with rifampin for 4 months may be recommended in this situation.

LTBI Treatment Regimens  Study Question 4.5

Introduce study questions

Ask participants to turn to p. 15 (if participants have print-based modules)

Read question 

Ask participants for answers

Answers – Module 4, p. 50

46

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	In what circumstances may LTBI treatment be given to people who have a negative TST or IGRA result? 

	Some contacts may start LTBI treatment if they have a negative TST or IGRA, but less than 8 to 10 weeks have passed since last exposed to TB; these contacts include:

Children who are younger than 5 years of age

People living with HIV

Special Considerations for LTBI Study Question 4.6

Read question 

Ask participants for answers

Note that expert consultation should be sought to determine if contacts with immune impairments other than HIV infection (e.g., contacts taking immunosuppressive therapies) could benefit from treatment even if they have a negative TST or IGRA result. 

Answers – Module 4, p. 50

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	What conditions must be met to stop LTBI treatment for children who are younger than 5 years of age and have been exposed to TB?

LTBI treatment can be stopped if ALL the following conditions are met:

Child is at least 6 months of age

Second TST or IGRA is negative

Second TST or IGRA was done 8 to 10 weeks after the child was last exposed to TB

Special Considerations for LTBIStudy Question 4.7

Read question 

Ask participants for answers

Answers – Module 4, p. 50

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations for LTBIStudy Question 4.8

	When should pregnant women be treated for LTBI and for how long? 

For most pregnant women with TB infection, LTBI treatment can be delayed until after delivery. If the pregnant woman is HIV-infected or a recent contact, immediate treatment should be considered. 

Preferred treatment regimen for pregnant women is 9 months of INH with a vitamin B6 supplement.

Read question

Ask participants for answers

Answers – Module 4, p. 51

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Treatment of Latent TB Infection (LTBI)Adverse Reactions and Patient Monitoring

Introduce section

Adverse Reactions and Patient Monitoring – Module 4, pp. 17-19

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Adverse Reactions to INH (1)

About 10% to 20% of people treated with INH will have mild, abnormal liver test results during treatment

In most people, liver test results return to normal 

51

Explain that some health care workers have concerns about treating patients for LTBI due to the length of treatment and the possibility of adverse reactions

Stress that, as with any treatment, the risks and benefits of LTBI treatment must be weighed for each individual

Review slide content 

Adverse Reactions – Module 4, p. 17

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Adverse Reactions to INH (2)Hepatitis

A major risk of INH is hepatitis (inflammation of the liver)

Hepatitis prevents the liver from functioning normally, causing symptoms such as:

Nausea

Vomiting

Abdominal pain

Fatigue

Brown urine

52

Review slide content 

Adverse Reactions – Module 4, p. 17

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Adverse Reactions to INH (3)Hepatitis

INH can cause hepatitis in anyone; however, hepatitis occurs in less than 1% of people taking INH 

Certain risk factors increase the risk of serious hepatitis, such as:

Older age 

Alcoholism

Review slide content 

Adverse Reactions – Module 4, p.17

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Adverse Reactions to INH (4)Peripheral Neuropathy

INH can cause peripheral neuropathy

Damage to sensory nerves of hands and feet

Symptoms include a tingling sensation, weakened sense of touch, or pain in the hands, palms, soles and feet

HIV, alcoholism, diabetes, and malnutrition increase risk for peripheral neuropathy

People with these conditions should be given vitamin B6

Review slide content 

Adverse Reaction – Module 4, p. 17

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Adverse Reactions to RIF, RPT, and RFB

Hepatitis is more likely to occur when RIF is combined with INH

Other side effects of RIF, RPT, and RFB include:

Rash

Gastrointestinal symptoms

Orange discoloration of urine, saliva, and tears

Interaction with many other drugs, such as birth control pills and implants, warfarin, some HIV drugs, and methadone

Hypersensitivity

55

Review slide content 

Explain that gastrointestinal symptoms may include abdominal pain, nausea, and anorexia

Note that orange discoloration is considered a minor reaction (not serious)

Adverse Reactions – Module 4, pp. 17-18

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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RPT may cause flu-like symptoms

RFB may cause

Eye inflammation

Joint pain

Lower white blood cell count

Adverse Reactions to RPT and RFB

56

Review slide content 

Adverse Reactions – Module 4, p. 18

Adverse Reactions

Patients should be instructed to report any signs and symptoms of adverse drug reactions to their health care provider

Patients should stop taking the medication and seek medical attention immediately if symptoms of serious adverse reactions occur

No appetite 

Nausea 

Vomiting 

Yellowish skin or eyes 

Fever for 3 or more days 

Abdominal pain 

Tingling in fingers and toes 

Brown urine 

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Review slide content 

Adverse Reactions – Module 4, p. 18 and Module 4, p. 33

Note: Adverse reactions to TB drugs are discussed more in-depth on slides 100-108

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patient Monitoring (1)

All persons taking LTBI treatment should be educated about symptoms caused by adverse reactions

Patients need to be evaluated at least monthly during therapy for:

Adherence to prescribed regimen 

Signs and symptoms of TB disease

Adverse reactions

58

Review slide content 

Stress that patients should be instructed to stop taking the medication and seek medical attention immediately if symptoms of serious adverse reactions occur

Patient Monitoring – Module 4, p. 18

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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During each monthly evaluation, patients should be:

Asked whether they have nausea, abdominal pain, or other symptoms of adverse reactions

Examined by HCW for adverse reactions

Instructed to stop medications and contact HCWs immediately if they have signs or symptoms of hepatitis

Patient Monitoring (2)

Review slide content

Patient Monitoring – Module 4, p. 18

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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People at greatest risk for hepatitis should have baseline liver function tests before starting LTBI treatment and every month during therapy. This includes:

People living with HIV

People with history of liver disorder or disease

People who use alcohol regularly

Women who are pregnant or just had a baby 

People taking medications that may increase risk of hepatitis

Patient Monitoring (3)

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Review slide content

Patient Monitoring – Module 4, p. 18

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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For all patients, INH, RIF, and RPT should be stopped if liver function test results are:

3 times higher than upper limit of the normal range and patient has symptoms

OR

5 times higher than upper limit of the normal range and patient has no symptoms

Patient Monitoring (4)

Review slide content

Patient Monitoring – Module 4, p. 19

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Patients should receive documentation of TST or IGRA results, treatment regimens, and treatment completion dates

Patients should present these documents any time they are required to be tested for TB infection

Patients should be re-educated about signs and symptoms of TB disease

LTBI Treatment Follow-Up

Review slide content

LTBI Treatment Follow-Up – Module 4, p. 19

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	Name 4 reasons why patients should receive a medical evaluation before starting LTBI treatment.

Exclude possibility of TB disease

Determine whether they have ever been treated for TB infection or TB disease

Identify any medical conditions that may complicate therapy or require more careful monitoring 

Establish and build rapport with patient

Medical Evaluation Study Question 4.9

Introduce study questions

Ask participants to turn to p. 20 (if participants have print-based modules)

Read question 

Ask participants for answers 

Answers – Module 4, p. 51

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	Why is it important to exclude the possibility of TB disease before giving a patient LTBI treatment? 

		Treating TB disease with LTBI treatment 	regimen (usually a single drug) can lead 	to drug resistance.

LTBI TreatmentStudy Question 4.10

Read question 

Ask participants for answers 

Answers – Module 4, p. 51

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	What are the symptoms of hepatitis? 

Nausea 

Vomiting

Abdominal pain

Fatigue

Brown urine

Adverse ReactionsStudy Question 4.11

Read question 

Ask participants for answers 

Answers – Module 4, p. 51

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Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	Who is at greatest risk for hepatitis?  What special precautions should be taken for these patients?

People with greatest risk for hepatitis are:

People living with HIV

People with a history of liver disorder or disease

People who use alcohol regularly

Women who are pregnant or just had a baby 

People who are taking other medications that may increase the risk of hepatitis

These patients should have liver function tests before starting LTBI treatment and during therapy		

Adverse ReactionsStudy Question 4.12

Read questions 

Ask participants for answers 

Answers – Module 4, p. 51

66

	How often should patients be evaluated for signs and symptoms of adverse reactions during LTBI treatment? 

All patients receiving LTBI treatment should be evaluated at least monthly during therapy. 

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Adverse ReactionsStudy Question 4.13

Read question 

Ask participants for answers 

Answers – Module 4, p. 52

67

68

Treatment of TB Disease

Introduce section

Treatment of TB Disease – Module 4, pp. 22-30

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Treatment of TB Disease (1) 

Treating TB disease benefits both the person who has TB and the community

Patient: prevents disability and death; restores health

Community: prevents further transmission of TB

TB disease must be treated for at least 6 months; in some cases, treatment lasts longer

69

Review slide content

Treatment of TB Disease – Module 4, p. 22

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Treatment of TB Disease (2)
| Intensive Phase    | First 8 weeks of treatment Most bacilli killed during this phase 4 drugs used                                            |
|--------------------|--------------------------------------------------------------------------------------------------------------------------|
| Continuation Phase | After first 8 weeks of TB disease  treatment Bacilli remaining after intensive  phase are treated with at least 2  drugs |
| Relapse            | Occurs when treatment is not  continued for long enough Surviving bacilli may cause TB  disease at a later time          |

Review slide content

Treatment of TB Disease – Module 4, p. 22

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Treatment of TB Disease (3)

Intensive phase should contain the following four drugs:

Isoniazid (INH)

Rifampin (RIF)

Pyrazinamide (PZA)

Ethambutol (EMB)

Example of pills used to treat TB disease. From left to right: isoniazid, rifampin, pyrazinamide, and ethambutol.

Review slide content

Note that when drug susceptibility results are available, clinicians may change the regimen accordingly

Treatment of TB Disease – Module 4, p. 22

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Treatment must contain multiple drugs to which organisms are susceptible

Treatment with a single drug can lead to the development of drug-resistant TB

Treatment of TB Disease (4)

72

Review slide content

Treatment of TB Disease – Module 4, p. 22

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Drug resistance can develop when patients are prescribed an inappropriate regimen

TB disease must be treated with at least 2 drugs to which bacilli are susceptible

Using only one drug can create a population of tubercle bacilli resistant to that drug

Adding a single drug to failing regimen may have the same effect as only using one drug

Preventing Drug Resistance (1)

73

Review slide content

Explain that when two or more drugs are used together, each drug helps prevent the emergence of bacilli that are resistant to the other drugs

Preventing Drug Resistance – Module 4, p. 23

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Preventing Drug Resistance (2)

Resistance can develop when patients do not take drugs as prescribed

Patients do not take all of their pills 

Patients do not take pills as often as prescribed

When this happens, patients may expose the bacilli to a single drug

Review slide content

Preventing Drug Resistance – Module 4, p. 23

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Factors that increase the chance of patient having or developing drug-resistant TB:

Patient does not take their medicine regularly and completely

Patient comes from an area of the world where drug-resistant TB is common

Malabsorption of drugs

Patient is a contact to someone with drug-resistant TB

Failure to improve on drug-susceptible regimen

Patient develops TB disease again after having taken TB medicine in the past

Preventing Drug Resistance (3)

Review slide content

Preventing Drug Resistance – Module 4, p. 23

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76

Treatment of TB DiseaseTreatment Regimens

Introduce section

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TB Treatment Regimens*

Table. 4.3
|         | INTENSIVE PHASE |                                                                        | CONTINUATION PHASE |                                                                           |                      |                                                                                                                                                                                                      |                                                                             |
|---------|-----------------|------------------------------------------------------------------------|--------------------|---------------------------------------------------------------------------|----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|
| Regimen | Drugs           | Interval and Doses(minimum duration)                                   | Drugs              | Interval and Doses(minimum duration)                                      | Range of total doses | Comments                                                                                                                                                                                             | Regimen effectiveness                                                       |
| 1       | INHRIFPZAEMB    | 7 days/week for 56 doses (8 weeks)or5 days/week for 40 doses (8 weeks) | INHRIF             | 7 days/week for 126 doses (18 weeks)or5 days/week for 90 doses (18 weeks) | 182 to 130           | This is the preferred regimen for patients with newly diagnosed pulmonary TB.                                                                                                                        | greater                               lesser                                |
| 2       | INHRIFPZAEMB    | 7 days/week for 56 doses (8 weeks)or5 days/week for 40 doses (8 weeks) | INHRIF             | 3 times weekly for 54 doses (18 weeks)                                    | 110 to 94            | Preferred alternative regimen in situations in which more frequent DOT during continuation phase is difficult to achieve.                                                                            |                                                                             |
| 3       | INHRIFPZAEMB    | 3 times weekly for 24 doses (8 weeks)                                  | INHRIF             | 3 times weekly for 54 doses (18 weeks)                                    | 78                   | Use regimen with caution in patients with HIV and/or cavitary disease. Missed doses can lead to treatment failure, relapse, and acquired drug resistance.                                            |                                                                             |
| 4       | INHRIFPZAEMB    | 7 days/week for 14 doses then twice weekly for 12 doses                | INHRIF             | Twice weekly for 36 doses (18 weeks)                                      | 62                   | Do not use twice-weekly regimens in HIV-infected patients or patients with smear positive and/or cavitary disease. If doses are missed then therapy is equivalent to once weekly, which is inferior. |                                                                             |

*For detailed information, refer to the Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

77

Ask participants turn to p. 24 for table 4.3 that describes recommended treatment regimens since it may be difficult to view the table on the slide (if participants have print-based modules)

Explain that there are several options for daily and intermittent therapy

TB Treatment Regimens – Module 4, p. 24

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Treatment of TB DiseaseStudy Question 4.14 

    Why must TB disease be treated for at least 6

    months? 

	Even though most bacilli are killed in the first 8 weeks, some bacilli can survive.  Therefore, treatment must continue in order to kill all remaining bacilli.

78

Introduce study questions

Ask participants to turn to p. 25 (if participants have print-based modules)

Read question 

Ask participants for answers

Answers – Module 4, p. 52

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  Which 4 drugs are recommended for the

  intensive phase of treatment for TB disease? 

		The intensive phase should include 	isoniazid, rifampin, pyrazinamide, and 	ethambutol.

Treatment of TB Disease Study Question 4.15

Read question 

Ask participants for answers

Answers – Module 4, p. 52

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    Why should multiple drugs be used to treat TB

   disease? 

	Using only one drug can create a population of tubercle bacilli that is resistant to that drug. When multiple drugs are used together, each drug helps prevent the emergence of bacilli that are resistant to the other drugs.

Treatment of TB Disease Study Question 4.16

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Ask for a volunteer to read question 

Ask participants for answers

Answers – Module 4, p. 52

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Drug ResistanceStudy Question 4.17

	Name 2 factors that can lead to drug resistance. 

	 Drug resistance can develop when:

Patients are prescribed an inappropriate regimen for treatment

Patients do not follow treatment regimens as prescribed

Read question 

Ask participants for answers

Answers – Module 4, p. 52

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82

Treatment of TB DiseaseSpecial Considerations

Introduce section

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TB medical experts should be consulted for complicated and challenging TB treatment issues

Consultation can be provided by State TB Programs and the CDC-funded TB Regional Training and Medical Consultation Centers (RTMCCs)

www.cdc.gov/TB/education/rtmc/default.htm

Special Considerations (1)

Review slide content 

Explain that the TB Regional Training and Medical Consultation Centers (RTMCCs) are regionally assigned to cover all 50 states and the U.S. territories

Tell participants that they may learn more about the RTMCCs by going to the website shown on the slide

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For HIV-infected TB patients receiving ART, the recommended treatment is a 6-month daily regimen consisting of:

An intensive phase of INH, RIF, PZA, and EMB for 2 months

A continuation phase of INH and RIF for 4 months

Special Considerations (2)People Living with HIV

Review slide content 

Explain that the management of HIV-infected TB patients is complex and therefore medical experts should be involved in the care and treatment of patients with HIV and TB

People Living with HIV – Module 4, p. 26

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ART should be initiated during TB treatment to improve treatment outcomes for TB patients living with HIV

ART should ideally be initiated  

Within 2 weeks of starting TB treatment for patients with CD4 cell counts <50/mm3

By 8 to 12 weeks of starting TB treatment for patients with CD4 cell counts >50/mm3

For patients with TB meningitis or TB involving the central nervous system, ART should NOT be initiated during the first 8 weeks of TB treatment 

Special Considerations (3)People Living With HIV

Review slide content 

People Living with HIV – Module 4, p. 26

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Special Considerations (4)People Living With HIV

It is important to be aware of the interaction of RIF with some ART drugs

Rifabutin has fewer drug interaction problems and may be used as a substitute for RIF for some patients

DOT should be provided for all TB patients living with HIV

For patients not receiving ART during TB treatment, it is recommended to extend treatment to 9 months

Review slide content 

People Living with HIV – Module 4, p. 26

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Treatment should begin as soon as TB disease is diagnosed

Regimen should consist of at least INH, RIF, and EMB for a minimum of 9 months

Clinicians should seek expert consultation to evaluate the risks and benefits of prescribing pyrazinamide (PZA) on a case-by-case basis

Streptomycin (SM) should NOT be used

Vitamin B6 supplements are recommended for all pregnant women taking INH

Special Considerations (5) Pregnant Women

87

Review slide content 

Explain that PZA should not be used because effects on the fetus are unknown

Explain that SM should not be used because it has harmful effects on the fetus

Pregnant Women – Module 4, p. 27

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Women being treated with first-line TB drugs should not be discouraged from breastfeeding

Only a small concentration of the drugs is found in breast milk

Not harmful to infant

Special Considerations (6) Breastfeeding

Review slide content 

Breastfeeding – Module 4, p. 27

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Special Considerations (7) Breastfeeding

Concentration of drugs in breast milk is not considered effective treatment for LTBI or TB disease for infant

Vitamin B6 supplements are recommended for all women who are taking INH and are breastfeeding

Review slide content 

Breastfeeding – Module 4, p. 27

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Special Considerations (8) Children

Children younger than 5 years of age should start TB treatment as soon as the diagnosis is suspected

Children can be treated with INH, RIF, PZA, and EMB for 2 months, followed by INH and RIF for 4 months

Children receiving EMB should be monitored for vision changes

A 3 drug regimen (INH, RIF, PZA)  can be considered in the intensive phase for children who are too young to have their vision monitored, are not infected with HIV, have no prior TB treatment history, and are not at risk for having drug-resistant TB

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Review slide content 

Children – Module 4, p. 27

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In general, regimens used for treating pulmonary TB are also effective for treating extrapulmonary TB 

9 to 12 month regimen is recommended for TB of the meninges or central nervous system 

6 to 9 month regimen is recommended for bone and joint TB

Special Considerations (9)People with Extrapulmonary Disease

Review slide content 

Note that extending treatment should be considered for patients with TB in any site that is slow to respond

People with Extrapulmonary Disease – Module 4, p. 28

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92

Treatment of TB DiseaseAlternative Regimens for Treating Drug-Resistant TB

Introduce section

92

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Alternative regimens should be used for treating drug-resistant TB 

Treatment of drug-resistant TB should always be done under the supervision of a medical expert 

Alternative Treatment Regimens (1)Drug-Resistant TB

Review slide content 

Drug-Resistant TB – Module 4, p. 28

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Alternative Treatment Regimens (2)Drug-Resistant TB

INH-resistant TB can be treated with the following regimen:

RIF, EMB, and PZA for 6 months

Review slide content 

Drug-Resistant TB – Module 4, p. 28

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MDR TB is resistant to INH and RIF, and is more difficult to treat than drug-susceptible TB

Drugs that can be used are less effective and are more likely to cause adverse reactions

Treatment can last 18 to 24 months after culture conversion

As a last resort, some patients undergo surgery to remove part of the disease site

Expert consultation should be sought

Alternative Treatment Regimens (3)MDR TB

Review slide content

Remind participants that MDR TB is resistant to both INH and RIF

Alternative Treatment Regimens – Module 4, p. 28

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Alternative Treatment Regimens (4)Extensively Drug-Resistant TB (XDR TB)

XDR TB is resistant to INH, RIF, plus any fluoroquinolone, and at least one injectable second-line drug (e.g., amikacin, kanamycin, or capreomycin)

XDR TB patients have less effective treatment options

XDR TB is very difficult to treat 

Expert consultation should be sought

Explain that XDR TB is a rare type of MDR TB

Review slide content 

Alternative Treatment Regimens– Module 4, p. 28

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Alternative Treatment Regimens (5)XDR TB

Successful outcomes for the patient depend greatly on:

Extent of drug resistance

Severity of disease

Whether the patient’s immune system is compromised

Review slide content 

Alternative Treatment Regimens – Module 4, p. 28

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Special Considerations Study Question 4.18

    What treatment regimen should be used for

    HIV-infected TB patients?

6-month daily regimen consisting of an intensive phase of INH, RIF, PZA, and EMB for 2 months followed by a continuation phase of INH and RIF for 4 months

ART should ideally be initiated 

Within 2 weeks of starting TB treatment for patients with CD4 cell counts <50/mm3

By 8 to 12 weeks of starting TB treatment for patients with CD4 cell counts >50/mm3

For patients with TB meningitis or TB involving the central nervous system, ART should NOT be initiated during the first 8 weeks of TB treatment 

98

Introduce study questions

Ask participants to turn to p. 29 (if participants have print-based modules)

Read question 

Ask participants for answers

Answers – Module 4, p. 53

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Special Considerations Study Question 4.19

    In what situations should treatment for TB disease last

    longer than the usual course of treatment?

HIV-infected TB patients need a minimum of 6 months of treatment. If an HIV-infected patient is NOT receiving ART during TB treatment, it is recommended to prolong treatment to 9 months. 

Pregnant women with TB disease should receive at least 9 months of treatment

Persons with TB disease of the meninges or central nervous system should receive a 9 to 12-month regimen

Persons with bone or joint TB disease should receive a 6 to 9-month regimen

Extending treatment should be considered for patients with TB disease in any site that is slow to respond

Treatment for MDR TB disease can last 18 to 24 months

99

Read question

Ask participants for answers

Answers – Module 4, p. 53

100

Treatment of TB DiseaseTreatment and Monitoring Plan and Adverse Reactions

Introduce section

100

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Every TB patient should have a specific treatment and monitoring plan developed in collaboration with local health department

Plan should include:

Description of treatment regimen

Methods of:

Monitoring for adverse reactions

Assessing and ensuring adherence to treatment

Evaluating treatment response

Treatment and Monitoring PlanTB Disease

Review slide content 

Note that the treatment and monitoring plan should be done within one week of suspected diagnosis

Treatment and Monitoring Plan – Module 4, p. 31

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Before starting treatment for TB disease, patients should have baseline blood and vision tests to detect problems that may complicate treatment

For example, patients who are taking ethambutol should have baseline visual acuity testing and testing of color discrimination

Monitoring Adverse Reactions (1)TB Disease

Review slide content 

Treatment and Monitoring Plan – Module 4, p. 31

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Monitoring Adverse Reactions (2)TB Disease

Follow-up tests should be done periodically if:

Results of baseline tests indicate abnormalities

Patient has symptoms that may be due to adverse reactions

Review slide content 

Monitoring Adverse Reactions – Module 4, p. 31

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Patients should be educated about symptoms caused by adverse reactions to drugs

Patients should be seen by clinician at least monthly during treatment and evaluated for possible adverse reactions

Public health workers who have regular contact with patients should ask about adverse reactions to treatment

Monitoring Adverse Reactions (3)TB Disease

Review slide content 

Explain that patients should also be educated about minor side effects of treatment; such as orange discoloration of urine from rifampin

Note that monitoring for adverse reactions must be individualized, depending on the drugs the patient is taking and the patient’s risk for adverse reactions

Monitoring Adverse Reactions – Module 4, pp. 31-32

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Monitoring Adverse Reactions (4)TB Disease

If patient has symptoms of a serious adverse reaction, HCWs should:

Instruct patient to stop medication

Report situation to clinician and arrange for medical evaluation

Note symptoms on the patient’s form

Review slide content 

Monitoring Adverse Reactions – Module 4, p. 32

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Adverse Reactions to TB Drugs (1)
| AdverseReaction | Caused by | Signs and Symptoms                                                                                                                                                                     | Significanceof Reaction* |
|-----------------|-----------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------|
| Allergic        | Any drug  | Skin rash                                                                                                                                                                              | May be serious or minor  |
| Eyedamage       | EMB       | Blurred or changed visionChanged color vision                                                                                                                                          | Serious                  |
| Hepatitis       | PZAINHRIF | Abdominal painAbnormal liver function test resultsBrown urine, light colored stoolFatigueFever for 3 or more daysFlu-like symptomsLack of appetiteNauseaVomitingYellowish skin or eyes | Serious                  |

Table. 4.4

106

Ask participants turn to p. 33 (if participants have print-based modules)

Explain that this table describes adverse reactions to TB drugs

Review slide content

Adverse Reactions to TB Drugs – Module 4, p. 33

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Adverse Reactions to TB Drugs (2)
| AdverseReaction       | Caused by | Signs and Symptoms                                      | Significance ofReaction* |
|-----------------------|-----------|---------------------------------------------------------|--------------------------|
| Nervous system damage | INH       | DizzinessTingling or numbness around the mouth          | Serious                  |
| Peripheralneuropathy  | INH       | Tingling sensation, numbness, or pain in hands and feet | Serious                  |
| Stomach upset         | PZA       | Stomach upsetVomitingLack of appetite                   | May be serious or minor  |
| Gout                  | PZA       | Abnormal uric acid      levelJoint aches                | Serious                  |

Table. 4.4

Review slide content

Adverse Reactions to TB Drugs – Module 4, p. 33

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| AdverseReaction                       | Caused by | Signs and Symptoms                                                                                                           | Significanceof Reaction* |
|---------------------------------------|-----------|------------------------------------------------------------------------------------------------------------------------------|--------------------------|
| Bleedingproblems due to low platelets | RIF       | Easy bruisingSlow blood clotting                                                                                             | Serious                  |
| Discoloration of body fluids          | RIF       | Orange urine, sweat, or tearsPermanently stained soft contact lenses                                                         | Minor                    |
| Druginteractions                      | RIF       | Interferes with many medications, such as birth control pills or implants, blood thinners, some HIV medicines, and methadone | May beseriousor minor    |

Adverse Reactions to TB Drugs (3)

Table. 4.4

*  Patients should stop medication for serious adverse reactions and consult a clinician immediately. Patients can continue taking medication if they have minor adverse reactions. 

Click to edit Master text styles

Second level

Third level

Fourth level

Fifth level

Review slide content

Adverse Reactions to TB Drugs – Module 4, p. 33

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    What should be included in each patient’s treatment plan?

Description of treatment regimen  

Methods of monitoring for adverse reactions

Methods of assessing and ensuring adherence to the treatment

Methods for evaluating treatment response	

TB Treatment and Monitoring PlanStudy Question 4.20

109

Introduce study questions

Ask participants to turn to p. 34 (if participants have print-based modules)

Read question 

Ask participants for answers

Answers – Module 4, p. 54

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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	Name the drug or drugs that may cause each of the following symptoms or adverse reaction. 

Nervous system damage: 

	INH

Hepatitis:  

	INH, PZA, RIF

Eye damage: 

	EMB

Orange discoloration of the urine: 

	RIF

Adverse Reactions to TB DrugsStudy Question 4.21

Read question 

Ask participants for answers

Answers – Module 4, p. 54

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	How often should patients be monitored for adverse reactions to TB drugs? 

	All patients should be seen at least monthly during treatment and evaluated for possible adverse reactions.

	Also, DOT providers should ask about any adverse reactions.

TB Treatment Monitoring Study Question 4.22

Read question

Ask participants for answers

Answers – Module 4, p. 54

111

112

Treatment of TB DiseaseAdherence and Evaluating Patients’ Response to Treatment

Introduce section

112

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113

Adherence to TB Treatment (1)

Most effective strategy to encourage adherence to treatment is DOT

Should be considered for ALL patients

Should be used for all children and adolescents 

Should be done at a time and place that is convenient for patients

113

Explain that in order to cure TB and prevent drug resistance, TB patients must adhere to treatment

Explain that adherence to TB treatment can be difficult because patients need to take several different medications for many months

Review slide content 

Ask participants what adherence problems they have encountered with patients and strategies they have used to overcome them

Adherence to TB Treatment – Module 4, p. 37

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Incentives and enablers can be used to improve patient adherence

Incentives are rewards given to patient, e.g., gift cards

Enablers help patient receive treatment, e.g., bus tokens

Adherence to TB Treatment (2)

114

Review slide content 

Explain that incentives are small rewards given to patients to encourage them to take their medicines or keep DOT appointments

Explain that enablers help patients receive treatment

Mention that incentives and enablers are generally offered along with DOT

Adherence to TB Treatment – Module 4, p. 38

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Adherence to TB Treatment (3)

Patients should be educated about TB disease and treatment

Cause of TB, transmission, diagnosis, and treatment plan

How and when to take medication

Review slide content 

Adherence to TB Treatment – Module 4, p. 38

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Patients not receiving DOT should be monitored for adherence to treatment:

Check if patient is reporting to clinic as scheduled

Ask about adherence

Ask patient to bring medications to clinic and count number of pills taken

Use urine tests to detect medication in urine

Assess patient’s clinical response to treatment

Monitoring Patients’ Adherence to Therapy

116

Review slide content 

Explain that none of these methods can be used to prove a patient took every dose of medication; the best way to ensure adherence to treatment is to use DOT

Monitoring Adherence to Therapy – Module 4, p. 38

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117

   Three methods to determine whether a patient

   is responding to treatment:

Check to see if patient has TB symptoms (clinical evaluation)

Conduct bacteriologic examination of sputum or other specimens

Use chest x-rays to monitor patient’s response to treatment

Evaluating Patients’ Response to Treatment (1)

117

Review slide content 

Evaluating Patients’ Response to Treatment – Module 4, pp. 39-40

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

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Evaluating Patients’ Response to Treatment (2)

Check to see if patient has TB symptoms (clinical evaluation)

TB symptoms should gradually improve and go away after starting treatment

Patients whose symptoms do not improve during the first 2 months of treatment, or whose symptoms worsen after initial improvement, should be reevaluated

Review slide content 

Explain that although each patient responds to treatment at a different pace, all patients’ TB symptoms should gradually improve

Evaluating Patients’ Response to Treatment – Module 4, pp. 39-40

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Evaluating Patients’ Response to Treatment (3)

2.   Conduct bacteriologic examination of sputum or other specimens

Specimens should be examined every month until culture results have converted from positive to negative

Any patient whose culture results have not become negative after 2 months of treatment, or whose results become positive after being negative, should be reevaluated

Review slide content 

Evaluating Patients’ Response to Treatment – Module 4, pp. 39-40

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Evaluating Patients’ Response to Treatment (4)

Use chest x-rays to monitor patient’s response to treatment

Repeated x-rays are not as helpful as monthly bacteriologic and clinical evaluations

Chest x-rays taken at end of treatment can be compared to any follow-up x-rays

Review slide content

Explain that chest x-rays can be useful for patients who have negative culture results before treatment

Evaluating Patients’ Response to Treatment – Module 4, pp. 39-40

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Evaluating Patients’ Response to Treatment (5)

TST or IGRA cannot be used to determine whether the patient is responding to treatment

Treatment completion is defined by number of doses the patient takes within a specific time frame

Length of treatment depends on drugs used, drug susceptibility test results, and the patient’s response to therapy

Review slide content 

Explain that most people who have a positive TST result will have a positive result again if they are skin tested later in their lives, regardless of whether they have received treatment 

Evaluating Patients’ Response to Treatment – Module 4, pp. 39-40

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Reevaluating Patients Who Do Not Respond to Treatment (1)

Reevaluating the patient means 

Obtaining a new specimen for TB culture, and (if positive) drug susceptibility testing

Assessing whether the patient has taken medication as prescribed

Reviewing symptoms

Performing a clinical examination

Repeating chest x-rays

Review slide content 

Reevaluating Patients Who Do Not Respond to Treatment – Module 4, p. 40

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Patients should be reevaluated if:

Symptoms do not improve in first 2 months of therapy

Symptoms worsen after improving initially

Culture results have not become negative after 2 months of treatment

Culture results become positive after being negative

Chest x-rays show worsening

Reevaluating Patients Who Do Not Respond to Treatment (2)

123

Review slide content 

Reevaluating Patients Who Do Not Respond to Treatment – Module 4, p. 40

Module 4 – Treatment of Latent Tuberculosis Infection and Tuberculosis Disease

124

	Name 4 ways clinicians can assess whether a patient is adhering to treatment. 

Check whether patient is reporting to clinic as scheduled

Ask patient to bring medications to each clinic visit and count the number of pills

Use urine tests to detect medication 

Assess patient’s clinical response to therapy

Adherence to TherapyStudy Question 4.23

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Answers – Module 4, p. 54

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	What is the best way to ensure that a patient adheres to treatment? 

Directly observed therapy (DOT)

Adherence to TherapyStudy Question 4.24

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	How can clinicians determine whether a patient is responding to treatment? 

Clinical evaluations

Bacteriologic evaluations

Chest x-rays 

Response to TreatmentStudy Question 4.25

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	Under what circumstances should patients be reevaluated? 

Symptoms do not improve during first 2 months of therapy

Symptoms worsen after improving initially

Culture results have not become negative after 2 months of treatment

Culture results become positive after being negative

Chest x-rays show worsening

Reevaluating the PatientStudy Question 4.26

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What does reevaluating the patient mean? 

	Reevaluating the patient means obtaining a new specimen for TB culture, and (if positive)  drug susceptibility testing, assessing whether the patient has been taking medication as prescribed, reviewing symptoms, performing a clinical evaluation, and repeating chest x-rays.

Reevaluating the PatientStudy Question 4.27

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Treatment of TB DiseaseRole of Public Health Workers

Introduce section

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Successful TB treatment is the responsibility of medical providers and HCWs, not the patient

Case management can be used to ensure that patients complete TB treatment

A health department employee is assigned responsibility for the management of specific patients

Role of Public Health Workers (1)

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Role of Public Health Workers – Module 4, pp. 43-44

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Provide DOT

Help monitor patients’ response to treatment

Educate patients and families about TB

Locate patients who have missed DOT visits or clinic appointments

Act as interpreters, arrange and provide transportation for patients, and refer patients to other social services

Work with private physicians to make sure TB patients complete an adequate regimen

Role of Public Health Workers (2)

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Role of Public Health Workers – Module 4, pp. 43-44

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	What is the goal of case management? 

To provide patient-centered care for completion of treatment and to ensure all public health activities related to stopping TB transmission are completed.

Role of Public Health Workers Study Question 4.28

Introduce study questions

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	What should a public health worker do if he or she notices that a patient has symptoms of a serious adverse reaction? 

Instruct patient to stop taking medication

Report situation to clinician and arrange for a medical evaluation right away

Note symptoms on patient’s form

Role of Public Health Workers Study Question 4.29

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Case Studies

Introduce case studies

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Module 4: Case Study 4.1 (1)

	You are sent to visit the home of a TB patient who was admitted to the hospital last week and diagnosed with infectious TB disease.  Living in the home are his wife and his 1-year-old daughter. Neither one has symptoms of TB disease. You give them both a TST and return 2 days later to read the results. You find that the wife has 14 mm of induration, but the daughter has no induration. 

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Case Study 4.1 – Module 4, p. 16

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	Should either one receive further evaluation for LTBI or TB disease? 

	Yes, both should receive further evaluation for LTBI or TB disease. 

Module 4: Case Study 4.1 (2)

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Should either one start LTBI treatment? Explain.

	Yes, both should start LTBI treatment. The wife is a contact of someone with infectious TB disease, and she has a positive TST. Therefore, after receiving a medical evaluation (and TB disease is ruled out), she should complete an entire course of LTBI treatment, regardless of her age.

Module 4: Case Study 4.1 (3)

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Answers – Module 4, p. 56

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Module 4: Case Study 4.1 (4)

Should either one start LTBI treatment? Explain.

(cont.)

	The daughter has a negative TST, but only one week has passed since her last TB exposure. It is possible that not enough time has passed for her to be able to react to the TST. 

	Since it is currently impossible to tell whether she has TB infection and because she may develop TB disease very quickly after infection, she should start LTBI treatment now and be retested 8 to 10 weeks after last exposure to TB. If negative upon retest, she may stop taking medicine. If positive, she should complete the entire course of LTBI treatment (9 months for children).

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Answers – Module 4, p. 56

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Module 4: Case Study 4.2 (1)

	A 65-year-old man is prescribed LTBI treatment with INH because he is a contact of a person with infectious TB disease and he has an induration of 20 mm to the TST. His baseline liver function tests are normal, but he drinks a six-pack of beer every day.

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Case Study 4.2 – Module 4, p. 21

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	What kind of monitoring is necessary for this patient while he is taking INH?

Although his liver function tests are normal, he is at high risk of INH-associated hepatitis because he is older and he abuses alcohol.

He should be educated about the symptoms of adverse reactions to INH and instructed to seek medical attention immediately if these symptoms occur.

He should be seen by a clinician monthly to ask about his symptoms, examine him for signs of adverse reactions, and consider performing liver function tests.

Module 4: Case Study 4.2 (2)

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Module 4: Case Study 4.3 (1)

An 18-month-old girl is admitted to the hospital because of meningitis. Doctors discover that her grandmother had pulmonary TB disease and was treated with a 6-month regimen. The medical evaluation of the child confirms the diagnosis of TB meningitis.  

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Case Study 4.3 – Module 4, p. 30

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Module 4: Case Study 4.3 (2)

	How long should the child be treated?

		The child should be treated for 9 to 12 	months because she has TB meningitis.

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Module 4: Case Study 4.4 (1)

You are assigned to deliver medications to TB patients as part of the DOT program where you work. When you visit Mr. Jackson’s house, you ask him how he is feeling. He tells you that he was up all night vomiting.  

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Case Study 4.4 – Module 4, p. 35

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Module 4: Case Study 4.4 (2)

	What are the possible causes? What should you do?

	His vomiting may be a symptom of 	hepatitis (caused by INH, RIF, and PZA) or 	of stomach upset due to PZA. Mr. 	Jackson should be advised to stop his 	medication, and the situation should be 	reported to the clinician immediately. Mr. 	Jackson should be given a medical 	evaluation right away.

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Module 4: Case Study 4.5 (1)

Ms. Young, a patient who started treatment for TB disease last week, calls the TB clinic to complain that her urine has changed to an odd color.  

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Case Study 4.5 – Module 4, p. 36

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Module 4: Case Study 4.5 (2)

Name 2 possible causes, and explain how each would affect the color of urine.

	One possible cause is the discoloration of body 	fluids, a common side effect of RIF. This would cause 	Ms. Young’s urine to turn orange. This is NOT a 	serious condition.

	Another possible cause is hepatitis, which can be 	caused by INH, RIF, or PZA. Hepatitis, a serious 	condition, would cause Ms. Young’s urine to turn 	dark. If Ms. Young’s urine is brown, the situation 	should be reported to the clinician and Ms. Young 	should receive a medical examination right away.

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Module 4: Case Study 4.6 (1)

Mr. Vigo was diagnosed with smear-positive pulmonary TB disease in January.  He was treated with INH, RIF, and PZA by his private physician.  He visited his physician again in March.  His drug susceptibility test results were not available at the time of this appointment.  Nevertheless, the physician discontinued his prescription of PZA and gave him refills of INH and RIF.  Mr. Vigo visited his physician again in April.  He had a persistent cough, and his sputum smear was found to be positive.  

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Case Study 4.6 – Module 4, p. 42

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Module 4: Case Study 4.6 (2)

What should be done next?

	Mr. Vigo’s persistent cough and positive sputum smear 	indicate that he is not responding to therapy. The most 	likely explanations are: 

He is not taking his medications as prescribed,

The regimen he has been prescribed is not adequate to treat his TB and he may have drug-resistant TB, or

A combination of the two factors listed above.

	The initial drug susceptibility test results should be located, 	and susceptibility tests should be repeated on a recent 	sputum specimen. In addition, his adherence should be 	evaluated, and he should be given DOT if possible.

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Module 4: Case Study 4.7 (1)

Ms. DeVonne began treatment for pulmonary TB disease 2 months ago, at the beginning of September.  You have been supervising her DOT.  During the first few weeks of therapy, you noticed that Ms. DeVonne’s symptoms were improving a little.  However, at a visit in October, you see that Ms. DeVonne is coughing up blood, and she tells you that she feels like she has a fever.  

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Case Study 4.7 – Module 4, p. 46

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Module 4: Case Study 4.7 (2)

What should you do?

	You should report her symptoms to the clinician and 	arrange for her to receive a medical evaluation right 	away. Also, you should note her symptoms on her record.

	Symptoms becoming worse after improving initially 	indicates that she is not responding to therapy. 	Because 	she is receiving DOT, she is probably taking her 	medications as prescribed. Therefore, the most likely 	explanation is that she has drug-resistant TB.

	Ms. DeVonne’s initial drug susceptibility test results 	should be located, and drug susceptibility tests should be 	repeated on a recent sputum specimen.

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Ask if there are any questions about Module 4 before moving on to Module 5

Answers – Module 4, p. 59

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